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In vitro survival and differentiation of neurons derived from epidermal growth factor-responsive postnatal hippocampal stem cells: inducing effects of brain-derived neurotrophic factor.

Publication ,  Journal Article
Shetty, AK; Turner, DA
Published in: J Neurobiol
June 15, 1998

Neural stem cells proliferate in vitro and form neurospheres in the presence of epidermal growth factor (EGF), and are capable of differentiating into both neurons and glia when exposed to a substrate. We hypothesize that specific neurotrophic factors induce differentiation of stem cells from different central nervous system (CNS) regions into particular fates. We investigated differentiation of stem cells from the postnatal mouse hippocampus in culture using the following trophic factors (20 ng/mL): brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and glial-derived neurotrophic factor (GDNF). Without trophic factors, 32% of stem cells differentiated into neurons by 4 days in vitro (DIV), decreasing to 10% by 14 DIV. Addition of BDNF (starting at either day 0 or day 3) significantly increased neuron survival (31-43% by 14 DIV) and differentiation. Morphologically, many well-differentiated neurons resembled hippocampal pyramidal neurons. 5'-Bromodeoxyuridine labeling demonstrated that the pyramidal-like neurons originated from stem cells which had proliferated in EGF-containing cultures. However, similar application of NT-3 and GDNF did not exert such a differentiating effect. Addition of BDNF to stem cells from the postnatal cerebellum, midbrain, and striatum did not induce these neuronal phenotypes, though similar application to cortical stem cells yielded pyramidal-like neurons. Thus, BDNF supports survival of hippocampal stem cell-derived neurons and also can induce differentiation of these cells into pyramidal-like neurons. The presence of pyramidal neurons in BDNF-treated hippocampal and cortical stem cell cultures, but not in striatal, cerebellar, and midbrain stem cell cultures, suggests that stem cells from different CNS regions differentiate into region-specific phenotypic neurons when stimulated with an appropriate neurotrophic factor.

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Published In

J Neurobiol

DOI

ISSN

0022-3034

Publication Date

June 15, 1998

Volume

35

Issue

4

Start / End Page

395 / 425

Location

United States

Related Subject Headings

  • Stem Cells
  • Neurons
  • Neurology & Neurosurgery
  • Mice, Inbred Strains
  • Mice
  • Hippocampus
  • Epidermal Growth Factor
  • Cells, Cultured
  • Cell Survival
  • Cell Line
 

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Shetty, A. K., & Turner, D. A. (1998). In vitro survival and differentiation of neurons derived from epidermal growth factor-responsive postnatal hippocampal stem cells: inducing effects of brain-derived neurotrophic factor. J Neurobiol, 35(4), 395–425. https://doi.org/10.1002/(sici)1097-4695(19980615)35:4<395::aid-neu7>3.0.co;2-u
Shetty, A. K., and D. A. Turner. “In vitro survival and differentiation of neurons derived from epidermal growth factor-responsive postnatal hippocampal stem cells: inducing effects of brain-derived neurotrophic factor.J Neurobiol 35, no. 4 (June 15, 1998): 395–425. https://doi.org/10.1002/(sici)1097-4695(19980615)35:4<395::aid-neu7>3.0.co;2-u.
Shetty, A. K., and D. A. Turner. “In vitro survival and differentiation of neurons derived from epidermal growth factor-responsive postnatal hippocampal stem cells: inducing effects of brain-derived neurotrophic factor.J Neurobiol, vol. 35, no. 4, June 1998, pp. 395–425. Pubmed, doi:10.1002/(sici)1097-4695(19980615)35:4<395::aid-neu7>3.0.co;2-u.
Journal cover image

Published In

J Neurobiol

DOI

ISSN

0022-3034

Publication Date

June 15, 1998

Volume

35

Issue

4

Start / End Page

395 / 425

Location

United States

Related Subject Headings

  • Stem Cells
  • Neurons
  • Neurology & Neurosurgery
  • Mice, Inbred Strains
  • Mice
  • Hippocampus
  • Epidermal Growth Factor
  • Cells, Cultured
  • Cell Survival
  • Cell Line